Lecture 4: Osteogenesis & ossification (Wronski)

Question 0

what are the 2 principal mechanisms for the formation of bone?

Answer 0

1. intramembranous ossification

2. endochondral ossification

Question 1

define osteogenesis or ossification

Answer 1

the formation of bone

Question 2

define intramembranous ossification

Answer 2

bone that forms within embryonic connective tissue

Question 3

define endochondral ossification

Answer 3

formation of bone within a hyaline cartilage model

Question 4

what type of bone is the first bone formed in both intramembranous and endochondral ossification?

Answer 4

cancellous (primary spongiosa). it is composed of trabeculae that can later be transformed into compact bone

Question 5

what are the 4 steps of intramembranous ossification?

Answer 5

1. osteoblasts differentiate within richly vascularized embryonic mesenchyme and produce thin strands of extracellular matrix - forming a network of osteoid trabeculae
2. osteoblasts and osteoprogenitor cells become aligned on the trabecular surfaces.
3. osteoblasts produce cytoplasmic processes that become embedded to form osteocytes within lacunae and canaliculi.
4. osteoprogenitor cells form new osteoblasts and additional matrix is laid down and calcified to form new lacunae and canaliculi

Question 6

define appositional growth

Answer 6

process of adding new bone upon pre-existing bone surfaces

Question 7

is interstitial growth of bone possible in intramembranous ossification? why or why not?

Answer 7

no; due to mineralization immediately following the deposition of bone matrix

Question 8

describe the characteristics of woven bone

Answer 8

• collagen fibers are randomly oriented*
• non-uniform distribution of osteocytes*
• it is formed during development or fracture repair
• is immature bone with a lower mineral content
• is eventually replaced with lamellar bone

Question 9

describe the characteristics of lamellar bone

Answer 9

• regularly arranged collagen fibers within lamellae*
• mature bone with high mineral content
• more uniform distribution of osteocytes
• structurally sound

Question 10

main difference between woven bone and lamellar bone

Answer 10

woven bone has randomly oriented collagen fibers and non-uniform distribution of osteocytes. it is considered inferior and eventually transforms to lamellar bone which is high in mineral content

Question 11

how can trabecular or cancellous bone be converted to compact bone?

Answer 11

by the deposition of repeating layers of new bone that encroach upon and largely fill the connective tissue spaces between trabeculae.

Question 12

are primary osteons in newly compact bone that was originally cancellous bone lamellar or woven in configuration?

Answer 12

these primary osteons are considered woven bone despite having lamellar configuration because the collagen fibers are not highly oriented within each lamina.

Question 13

how does the initial cartilage model develop?

Answer 13

from differentiation of mesenchymal cells into chondroblasts that produce matrix and perichondrium.

Question 14

what type of growth is applied to the cartilage model?

Answer 14

both appositional and interstitial growth!

Question 15

what are the 8 steps in forming the primary (diaphyseal) center of ossification?
(didn’t know how to break this one up, sorry!)

Answer 15

1. the surrounding matrix of the hypertrophy of chondrocytes in the diaphysis becomes calcified,
2. chondrocytes and cartilage matrix degenerate so that large cavitations of confluent lacunae are formed.
3. perichondrium transforms to periosteum as mesenchymal cells of the diaphysis differentiate into osteoblasts and form a subperiosteal collar of bone around the diaphysis (this is a form of intramembranous ossification)
4. projections of tissue containing blood vessels, stem cells, and osteoprogenitor cells invade the cavitations of the cartilage model and form a primary center of ossification
5. osteoprogenitor cells differentiate into osteoblasts and produce bone matrix
6. trabeculae of cancellous bone is formed
7. osteoclasts remove cancellous bone within the center of ossification to form a medullary cavity
8. the periosteal bud provides osteoprogenitor cells and stem cells that form endosteum and myeloid tissue of bone marrow

Question 16

how does developing bone lengthen via endochondral ossification?

Answer 16

via interstitial growth of hyaline cartilage at the epiphyses.

Question 17

what does the growth plate leave behind as it continues to grow?

Answer 17

as it advances, it leaves behind cartilage cores and bone is deposited on the surface of cartilage cores, this is considered rudimentous or cancelous bone.
keep in mind there is also remodeling and resorption going on along the surface.

Question 18

ossification of the epiphyses extends in all directions to form cancellous bone except for 2 regions. what are they?

Answer 18

1. articular cartilage - covering the articular surface

2. the epiphyseal growth plate - a plate of hyaline cartilage between the epiphysis and metaphysis

Question 19

what is another term for the growth plate?

Answer 19

the physis

Question 20

what is the metaphysis?

Answer 20

the enlarged portion of the diaphysis that abuts the epiphyseal plate

Question 21

how many centers of ossification do most long bones develop?

Answer 21

2 :-)

Question 22

how many centers of ossification do most short bones develop?

Answer 22

only one :-(

Question 23

how is the principal increase in bone length achieved?

Answer 23

by elongation of the metaphysis and diaphysis at the epiphyseal growth plate

Question 24

following the formation of primary and secondary centers of ossification, bone growth and elongation involves 2 main processes. what are they?

Answer 24

1. interstitial growth of epiphyseal plate cartilage along the epiphyseal margin
2. endochondral ossification of cartilage at the metaphyseal margin

Question 25

there are 4 zones of the epiphyseal growth plate. what are they?

Answer 25

1. zone of resting cartilage
2. zone of proliferating cartilage
3. zone of maturing and hypertrophying cartilage
4. zone of calcifying cartilage

Question 26

what is the zone of resting cartilage?

Answer 26

it is composed of chondrocytes nearest the epiphyseal bone tissue and serves to anchor the plate to the bony epiphysis

Question 27

what is the zone of proliferating cartilage?

Answer 27

it is composed of dividing chondrocytes arranged in columns

Question 28

what is the zone of maturing/hypertrophying cartilage?

Answer 28

it is composed of hypertrophied chondrocytes arranged in columns

Question 29

what is the zone of calcifying cartilage?

Answer 29

it is composed of calcified cartilage :-P

Question 30

as bone length increases, how does the bone maintain is proportion? length relative to width?

Answer 30

as new bone is formed at the metaphysis, the trabeculae at the periphery of the epiphyseal plate become added to the shaft as the bone grows in length.

the width of the added shaft at the metaphysis is maintained by resorption of bone by osteoclasts at the periphery thereby reducing the diameter to match the diaphysis

Question 31

how does bone diameter increase? what is this an example of?

Answer 31

appositional bone growth occurs at the periosteal surface of the diaphysis, adding successive layers of new bone. simulatenously, bone resoprtion occurs at the endocortical surface to maintain and expand the medullary cavity.

this is a classic example of bone remodeling

Question 32

how does bone growth stop?

Answer 32

cartilage cell proliferation eventually stops in the epiphyseal plate. the epiphyseal plate then disappears resulting in confluence of trabeculae and cavities of the epiphysis and metaphysis. following closure, longitudinal bone growth is no longer possible.

Question 33

what two hormones affect bone growth? how?

Answer 33

estrogen and growth hormone

growth hormone stimulates chondrocyte proliferation within the growth plate
estrogen inhibits chondrocyte proliferation

Question 34

define osteoporosis

Answer 34

low bone mass that results in bone fractures after only minimal trauma.

Question 35

which sites are the most common for bone fractures?

Answer 35

hip (femoral neck), thoracic and lumbar vertebral bodies and the wrist

Question 36

what is the most important factor influencing development of postmenopausal osteoporosis?

Answer 36

estrogen deficiency

Question 37

describe the early stages of postmenopausal osteoporosis

Answer 37

• rapid bone loss (primarily cancellous bone)
• increased bone formation
• greater increase in bone resoprtion due to hyperactive osteoclasts

Question 38

describe the late stages of osteoporosis

Answer 38

• slow bone loss
• decreased bone formation
• normal bone resorption

Question 39

what are some (duh) factors affecting the development of osteoporosis

Answer 39

• estrogen deficiency
• genetic predisposition
• sedentary lifestyle
• smoking
• low dietary calcium

Question 40

describe some treatements for postmenopausal osteoporosis

Answer 40

• anti-resorptive agents (like estrogen, calcitonin, biphosphates, etc.)
• anabolic agents to stimulate bone formation like sodium fluoride (it induces formation of woven bone and is not approved by the FDA)
• Parathyroid hormone

Question 41

which animal can experience nutritional osteodystrophy (bone breakdown due to low dietary calcium)

Answer 41

iguanas!

Question 42

what are some clinical signs of nutritional osteodystrophy

Answer 42

• muscle twitching a.k.a. tetany
• pathologic bone fractures
• diaphyseal enlargements of long bones
• widened growth plates in growing animals (inconstant)